Diagnostic formulation for ph determination



United States Patent 3,122,420 DIAGNGEITEC FGRMULAETGN non pH DETERMFNATEGN Eehn Rehar, 3L, and Paul W. 'Clalres, Elhhart, End, and Wayne A. Freeby, ldaho Falls, Idaho, assrgnorsto lvliles Laboratories, The, .Elithart, ind, a corporation o Indiana i le Drawing. Filed Feb. 28, E62, Ser. No. 176,454 5 *Jlaims. (Cl. 23253) This invention relates to new and improved diagnostic composition. Particularly the invention relates to diagnostic compositions which are useful for the quantitative determination of the hydrogen ion concentration in fluids, particularly body fluids such as urine. More especially, it embraces a pH indicator test for use 1n combination with one or more other tests, 1.e glucose, albtunin, etc., all of which may be performed in a single dip and read operation.

A pH determination, to be of greatest value, must be conveniently rapid, dependable and sunple enough for the technician to use with ease, accurate enough to serve the clinician, and sensitive enough to reflect variations in the patients condition. Moreover, the reagent composition must be adequately stable.

We have now found a new formulation for preparing the pH test portion of a dip and read type of indicator test strip which oifers a superior means for investigating biological fluids for their hydrogen ion concentration. This unique pl-l test mixture comprises an indicator material which in the form of a solution is used to 1mpregnate a desired portion of the bibulous carrier. I

The pl-l test area of such a combination test stick has heretofore been prepared according to a formula which included various indicators, alcohol, wetting agents and polyvinyl alcohol in aqueous solution.

This formulation was unsatisfactory, however, with respect to the drying time an temperature range which was reouired to adequately dry the pH test area. Temperatures had to be varied between 75 and 80 C. and a minimum drying time of about 8 minutes was required. Frequently, moreover, the sticks were still wet at the end of the 8 minute period and the drying time had to be increased to 11 minLtes.

Another disadvantage of this coloration of the test po .ion of the stick which resulted from the high temperatures used drying. iarticularly in diagnostics containing several test portions high tem peratures were used in order to dry all of the reagents on the stick in one operation. A large percentage of the sticks containing the above type of formulation were rejected because of the undesirable color resulting from such processing steps.

Since polyvinyl alcohol was believed to be responsible for discoloration of the previously used formulations, a new formulation was prepared by replacing the polyvinyl alcohol with certain other ingredients which are capable of imparting stability and improved color to the test area. It was found that the desired color uniformity and stability could be produced by a novel mixture of three ingredients in addition to the previously used indicators, wetting agents and alcohol. These ingredients are:

formulation was a dis (1) Bodying and stabilizing agent (2) Color dispersing agent (3) Color intensifying agent The body and stabilizing agent selected for use in these diagnostic formulations is a refined extract of car rageen, sometimes referred to as Irish moss. From it, most of the metallic ions present in Irish moss have been eliminated with the exception of the sodium ion. Thus,

3,122,420 Patented Feb. 25, 1954 this ingredient is in effect, substantially a sodium carrageenate. It has an externally low chloride content ad forms clear viscous solutions without the usual gel formation induced by temperature changes which is typical of regular Irish moss extracts.

The color dispersing agent may be any polymeric material which is soluble in aqueous solution and which has the property of giving a uniform color dispersion when added to dye formulations. Particularly preferred for this purpose is polyvinyl pyrrolidone.

The color intensifying ingredient is one which gives the color a brighter hue. For this purposeit has been found desirable to utilize a polyalkylene glycol. Various polyalkylene glycols are commercially available. Lower polyalkylene glycols have been found particularly useful for this purpose and in particular polyethylene glycol. Selection of a particular polyalkylene glycol will of course be decided by considerations of solubility as well as the color intensity obtained by the use of various polyalkylene glycols.

The above described three ingredients, which are primarily responsible for the results obtained in the use of the formulations of this invention are used in conjunction with a pH indicator, preferably one which will produce color changes in the range of about from pH 5 to pH 9. For this purpose various indicator dyes and combinations may be utilized. One found satisfactory is a mixture of Methyl Red and Bromthymol Blue. A mixture of these two ingredients in a proportion of one part Methyl Red to twenty parts Bromthyrnol Blue has been found particularly effective. Various other indicator combinations may be used if desired.

A Wetting agent is also utilized in preparing the formulations of this invention. Various types of wetting agents are satisfactory for this purpose.

The ingredients are finally dissolved in an aqueous lower aliphatic alcohol solution, for example an ethanolic solution.

The above described formulation is most advantageously used by absorbing the formulation upon a bibulous carrie For this purpose, paper strips or other suitable bibulous materials may be used. Following the absorption of the formulation by the bibulous carrier, the resulting test strips are dried at temperatures in the range of about from C. to 105 C. for a period of about from 5 to 10 minutes. Upon cooling, the strips are then ready for use in the form of dip and read diagnostic strips.

This invention will be better understood by reference to the following example. It is included merely for purposes of illustration, however, and is not to be construed as in any way unduly limiting the scope of the invention which is defined in the claims appended hereto.

Example The following materials were mixed together and bibulous paper strips impregnated therewith by dipping the strips into the mixture.

(Average molecular weight 4500.)

After dipping, the strips ere dried for seven minutes at a temperature of C. plus or minus 5 C.

These strips after cooling were tested in solutions of known pH. The colors observed at various hydrogen ion concentrations were as follows:

The advantages of the formulations of this invention exemplified by the example above reside not only in the ease of formulation, but also in the stabilizing of the resulting diagnostic sticks under relatively severe conditions of heat and humidity. In addition, the colors developed can be readily distinguished at various pH ranges and are of an intense enough hue to be easily read. Use of a color chart, for example, will enable the user of these sticks to accurately determine the pH of the solution, such as urine, being tested.

In summary, this invention provides a novel formulation which is utilized in a composition for determining the pH of various solutions including biological fluids such as urine. The formulation contains in addition to the necessary indicator, wetting agent and alcoholic base, a mixture of a bodying and stabilizing agent such as a refined carrageen extract, a color dispersing agent such as polyvinyl pyrrolidone and a color intensifying agent such as a polyalkylene glycol.

What is claimed is:

l. A diagnostic composition for use in determining the hydrogen ion concentration of biological fluids which comprises an indicator composition which exhibits a color change upon being subject to a change in hydrogen ion concentration, a refined carrageen extract, polyvinyl pyrrolidone and a polyalkylene glycol impregnated upon a bibulous carrier.

2. A product according to claim 1, wherein the indicator composition consists of a mixture of Methyl Red and Bromthymol Blue in a proportion or" about 1 part Methyl Red to 20 parts Eromthyrnol Blue.

3. A product according to claim 1 wherein the polyalkylene glycol is a polyethylene glycol.

4. A product according to claim 1, wherein the refined carrageen is substantially a sodium carrageenate.

5. A diagnostic composition for use in determining the hydrogen ion concentration in human urine which comprises about 1 part Methyl Red, about 20 parts Bromthyrnol Blue, about parts of a refined carrageen extract, about 230 parts polyvinyl pyrrolidone and about 230 parts of a polyethylene glycol having an average molecular weight of about 4500, all impregnated upon a bibulous carrier.

References Cited in the file of this patent UNITED STATES PATENTS 2,567,445 Parker Sept. 11, 1951 

1. A DIAGNOSTIC COMPOSITION FOR USE IN DETERMINING THE HYDROGEN ION CONCENTRATION OF BIOLOGICAL FLUIDS WHICH COMPRISES AN INDICATOR COMPOSITION WHICH EXHIBITS A COLOR CHANGE UPON BEING SUBJECT TO A CHANGE IN HYDROGEN ION CONCENTRATION, A REFINED CARRAGEEN EXTRACT, POLYVINYL PYRROLIDONE AND A POLYALKYLENE GLYCOL IMPREGNATED UPON A BIBULOUS CARRIER. 